We intend to establish a Center for Children's Environmental Health and Disease Prevention Research at U.C. Davis that will investigate environmental risk factors contributing to the incidence and severity of childhood autism. Autism is a neurodevelopmental disorder defined by deficiencies of social reciprocity and communication, and by repetitive behavior, The majority of cases seem likely to arise from a multiplicity of yet unidentified genetic and environmental factors. Surveys in California have indicated an apparent 210% increase in the cases of profound autism in children diagnosed over the last 10 years. Recent estimates indicate the frequency of mild to severe autism may be as high as 1:150. Thus there is growing concern from both parents and health professionals that prenatal and postnatal exposure to xenobiotic (e.g. mercurials, halogenated aromatics, and pesticides) and biotic (e.g. vaccine antigens) factors may act synergistically with unidentified susceptibility genetic factors to produce autistic spectrum disorders. To understand how the interaction of susceptibility genes with exposure to "environmental" chemicals may increase the risk and severity of autism and to identify which combination of chemical exposures confer the greatest threat, we propose to establish an interdisciplinary Center that addresses this complex problem at several levels. Project I proposes the first case-controlled epidemiological study of environmental factors in the etiology of autism. Tissue samples and exhaustive information will be collected from geographically distinct areas of California. Project two proposes to identify for the first time how known neurotoxicants of concern to children's health influence the development of social behavior and mediating brain regions such as the amygdala. Project III integrates elements of Projects I and II in order to examine molecular mechanisms underlying neurodevelopmental disorders associated with human autism and animal models of autism. The three research projects are integrated within a center framework that provides extensive facility core capabilities in xenobiotic/lipid analysis (Core I), cell activation biomarkers (Core II), and molecular biomarkers (Core III). Our ultimate goal is to understand common patterns of dysfunction in autism and elucidate mechanisms by which known neuroimmunotoxicants contribute to abnormal development of social behavior in children so that rational strategies for treatment and prevention can be undertaken.